1. Field of the Invention
This invention relates to 4-phenyl-1,4-dihydropyridine derivatives which are useful in the treatment of cardiovascular diseases such as hypertension, congestive heart failure, angina, migraine, and vasospastic disorders. The invention also relates to a pharmaceutically acceptable composition containing an effective amount of at least one of the compounds in combination with a suitable excipient, the composition being useful for the treatment of cardiovascular diseases such as hypertension, congestive heart failure, angina, migraine, and vasospastic disorders in mammals. The invention also relates to a process for making the compounds of the invention, and the use of compounds of the invention in pharmaceutical compositions useful for the treatment of cardiovascular diseases such as hypertension, congestive heart failure, angina, migraine, and vasospastic disorders in mammals.
The invention also relates to intermediates and processes for preparing optically active compounds of the invention.
2. Related Disclosures
Certain 4-aryl-1,4-dihydropyridine derivatives are known calcium entry antagonists. See, for example, U.S. Pat. Nos. 3,485,847 and 4,044,141. Novel 4-phenyl-1,4-dihydropyridine derivatives with high efficacy and long duration of action have now been prepared.
It is known that, for most cardiovascular-active dihydropyridine derivatives, the isomer which has an (S) configuration at C4 in the dihydropyridine ring is more active than the (R) isomer. Compounds with the (S) configuration may be prepared from (-)-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyr idine. This (S) isomer may be prepared following the method of T. Shibanuma, et al., Chem. Pharm. Bull., 28, 2809-2812 (1980). Now, a more efficient, effective, and less expensive method for preparing optically active mono-esterified dihydropyridine derivatives has been discovered.